Many different techniques to sort, position, and transport microscopic particles exist currently. For example, particles can be trapped in a high-intensity optical field and transported by moving that field as is disclosed in Mio, C. et al. Rev. Sci. Instrum., 2000, 71, 2196. Other known methods employ electric fields, see e.g. Velev O. et al., Langmuir 1999, 15, 3693. While such methods in general are used for transport across relatively small distances, it is also known to apply holographic maps to transport particles across larger distances, see Liesner J. et al., Opt. Comm. 2000, 185, 77.
From Yellen, B. B. et al., J. Appl. Phys. 2003, 93, 7331, a concept of using topographic magnetic patterns for the transport of individual magnetic or non-magnetic particles is known. The patterns can for example be ellipses or rectangles and the particles are transported by means of superposition of the stray fields of these patterns with external homogeneous or inhomogeneous fields. The known topographic patterns are fabricated from a ferromagnetic material and the shape anisotropy of the patterns induces a defined easy magnetization axis along which the pattern magnetization can be easily switched by low external magnetic fields. In this concept, single superparamagnetic particles may be transported from one topographic pattern to the next. Moreover, as disclosed in Halverson, D. et al., J. Appl. Phys. 2006, 99, 08P504, non-magnetic particles may be transported by exploiting variations in the density of a ferrofluid in a combination of a local stray field and an external field. Since in these concepts usually the size of a magnetic pattern is close to the dimension of the particle to be transported, in some cases this may be too large to transport biomolecules in living cells.
In U.S. Pat. No. 7,760,529 B2 a system for the transport of paramagnetic particles is disclosed, which comprises a magnetic garnet film having a plurality of magnetic domain walls, and a liquid solution on a surface of the magnetic garnet film, wherein the liquid solution includes a plurality of paramagnetic particles. The garnet film is provided with a natural domain pattern, the domain magnetization being perpendicular to the plane of the film. An external field is applied to transport at least a portion of the paramagnetic particles from one magnetic domain wall to another.
The transport of biomolecules by means of superparamagnetic particles to which they are attached is an active field of research. For example, the detection of such particles by magnetoresistive sensors appears promising in biotechnological applications. Baselt D. R. et al. in Biosensors Bioelectron. 1998, 13, 731 used a BARC (bead array counter) sensor to analyze DNA through a defined coupling of beads (functionalized with a receptor molecule) to DNA fragments immobilized on the surface of a sample. Subsequently several different concepts for biosensors based on spin valves (see e.g. Edelstein R. L. et al., Biosensors Bioelectron. 2000, 14, 805), Hall sensors (see e.g. Ejsing L. et al., J. Magn. Magn. Mat. 2005, 293, 677) or magnetoresistive sensors (see Wang. S. et al. J. Magn. Magn. Mat. 2005, 293, 731, 21), as well as some concepts for a guided movement of magnetic particles (see e.g. Gunnarsson K. et al., Adv. Matter, 2005, 17, 1730) have been tested. The inhomogeneous magnetic fields necessary for the transport of the particles have been created by macroscopic external coils and yokes as e.g. disclosed in Bausch A. R. et al., Biophys. J. 1999, 76, 573 or via currents through strip lines as e.g. disclosed in Ferreira H. A. et al., J. Appl. Phys. 2003, 93, 7281. The use of currents in strip lines enabled the control of local inhomogeneous magnetic fields, through which a particle transport may be controlled and a particle positioning achieved.
Schotter J. et al. in IEEE Trans. Mag. 2002, 38, 3365 have disclosed a biosensor chip based on the detection of functionalized magnetic nanoparticles via a magneto resistive sensor. This sensor consists of a spiral sensor strip, extending over a circular area of 75 μm diameter. The area corresponds to the typical area covered by droplets of pen spotted or ink jetted solutions used in modern techniques of biotechnology. Fundamental experiments have also been carried out to manipulate magnetic nanoparticles by currents through strip lines (see e.g. Breszka M., M. et al., J. Biotechnol. 2004, 112, 25) and they have shown that the sensitivity of magneto resistive detection is superior to that of optical detection using fluorescence markers (see also Schotter J. et al., Biosensors Bioelectr. 2004, 19, 1149). It has been shown that the magnetic force exerted on the superparamagnetic particles by currents through strip lines may be used for extremely sensitive bond force measurements of ligand receptor pairs.
Extremely low loading rates have been realized being superior to those in pulling experiments by atomic force microscopes, see Panhorst M. et al., Biosens. Bioact. 2005, 20, 1685. These experiments demonstrate nicely the possibility to integrate magnetic gradient field driven transport with sensing by magnetoresistive sensors.